Defining head and neck squamous cell carcinoma (HNSCC) prognostic and predictive biomarkers is anticipated to provide insights Into molecular contributors to disease progression and to contribute to HNSCC disease control. An ongoing effort by the Head and Cancer Program at the University of Pittsburgh has collected peripheral blood DNA from HNSCC cases and controls and demographic and tobacco use data beginning In 2000; tumor tissues have also been archived. Clinical, pathologic, and follow-up data continues to be collected for these 790 HNSCC cases. In addition to this large specimen and data collection, we have high-through-put genomic and proteomic technologies and expertise. We are therefore uniquely poised to evaluate biomarkers associated with HNSCC risk and prognosis. Epidermal growth factor receptor (EGFR) and gastrin-releasing peptide receptor (GRPR) are strongly implicated In HNSCC development/progression. Dr. Egloff proposes to: (1) determine whether EGFR/GRPR genetic variants are related to developing HNSCC using a case-control study; (2) determine whether EGFR/GRPR polymorphisms are prognostic indicators for HNSCC; and (3) evaluate correlations between HNSCC protein levels and EGFR/GRP R variant genotypes. These studies will be carried out with a carefully selected team of mentors and advisors who will provide expertise and guidance covering all aspects of the proposed studies. Dr. Egloff is an Assistant Professor in the Department of Otolaryngology, University of Pittsburgh with experience in translational research and formal training in cancer epidemiology and genetics. The candidate has outlined a career development plan including formal training in statistical genetics designed to facilitate her transition to an independent molecular epidemiologist cancer researcher. RELEVANCE (See instructions): The proposed studies will test the overall hypothesis that EGFR and GRPR genetic variants contribute to HNSCC risk and disease progression and are designed to gain insights into the molecular etiology of HNSCC and to define populations at risk for developing HNSCC and/or worse disease prognosis. Results of these studies are anticipated to inform treatment decisions and contribute significantly to HNSCC disease control.